First-episode psychosis at the West Bologna Community Mental Health Centre: results of an 8-year prospective study.

BACKGROUND: Research mostly conducted in the UK and northern Europe has established that there are high rates of first-episode psychosis (FEP) in large cities and immigrant populations; moreover, psychosis has been found to be associated with cannabis use and early trauma. The present study aimed to evaluate the incidence rate of FEP and the distribution of several risk factors (e.g. age, ethnicity, substance abuse) in Bologna, Italy. METHOD: The Bologna FEP (BoFEP) study is an 8-year prospective study. All FEP patients, 18-64 years old, consecutively referred to the West Bologna Community Mental Health Centre (CMHC) from 2002 to 2009 were evaluated. Sociodemographic information, migration history and clinical data were collected through an ad-hoc schedule. Psychiatric diagnoses were recorded using the Schedule for Clinical Assessment of Neuropsychiatry (SCAN). RESULTS: The overall incidence rate (IR) in the BoFEP study was 16.4 per 100 000 person-years [95% confidence interval (CI) 13.9-18.9]. The incidence was higher in young people, men and migrants (MI). CONCLUSIONS: The IR of FEP found by the Bologna study is lower than that found by other European studies. However, as in other studies, the incidence was higher in certain groups. This heterogeneity has implications for policy and mental health service development, and for understanding the aetiology of psychosis.

Parallel manifestations of neuropathologies in the enteric and central nervous systems.

BACKGROUND: Neurodegenerative diseases may extend outside the central nervous system (CNS) and involve the gastrointestinal (GI) tract. The gut would appear to be a pathological marker for neurodegeneration, as well as a site for studying the pathophysiology of neurodegeneration. In fact, both in the ENS and CNS, misfolded proteins are likely to initiate a process of neurodegeneration. For example, the very same protein aggregates can be detected both in the ENS and CNS. In both systems, misfolded proteins are likely to share common cell-to-cell diffusion mechanisms, which may occur through a parallel prion-like diffusion process. Independently from the enteric or central origin, misfolded proteins may proceed along the following steps, they: (i) form aggregates; (ii) are expressed on plasma membrane; (iii) are secreted extracellularly; (iv) are glycated to form advanced glycation end-products (AGEs); (v) are internalized through specific receptors placed on neighboring cells (RAGEs); (vi) are cleared by autophagy; and (vii) are neurotoxic. These features are common for a-synuclein (in Parkinson's disease and other synucleinopathies), ß-amyloid and tau (in degenerative dementia), SOD-1 and TDP43 (in amyotrophic lateral sclerosis), and PrPsc (in prion diseases). While in some diseases these features are common to both ENS and CNS, in others this remains a working hypothesis. PURPOSE: This review analyzes GI alterations from a pathological perspective to assess whether the enteric nervous system (ENS) mirrors the neuropathology described in the CNS. We discuss the potential mechanisms that lead to the onset and spread of neurodegeneration within the gut, from the gut to the brain, and vice versa.

Behavioural sensitisation during dopamine replacement therapy in Parkinson's disease is reminiscent of the addicted brain.

The intermittent oral intake of the dopamine (DA) precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is the classic therapy of Parkinson's disease (PD). In this way, the drug precursor can be metabolised into the active neurotransmitter DA. Although this occurs throughout the brain, the therapeutic relief is believed to be due to restoring extracellular DA levels within the dorsal striatum (more in the putamen than the caudate nucleus) which lacks endogenous DA as a consequence of the disease process. However, differing from physiological DA transmission, this therapeutic pattern leads to abnormal peaks of non-synaptic DA, which are supposed to trigger behavioural sensitisation expressed as abnormal involuntary movements. A similar pattern of abnormal DA stimulation occurs during methamphetamine (METH) intake. In the present review we will provide evidence showing the similarities between METH- and L-DOPA-induced DA stimulation with an intact and denervated striatum respectively. This comparison will encompass various features; the timing, the areas and the amount of extracellular DA levels which reveal surprising homologies. Such an overlapping between L-DOPA in PD and METH will be further analysed to critically assess the commonalities concerning the following points: abnormal receptor stimulation, recruitment of altered transduction pathways, abnormal gene expression, alterations in the phenotype of striatal neurons, and the establishment of behavioural sensitisation which appear as distinct phenomena (i.e. abnormal involuntary movements in PD and drug addiction in METH abuse); nonetheless, this may also lead to common behavioural alterations (METH-like addictive behaviours in PD patients during the course of DA replacement therapy in subsets of PD patients).

Methylated tin toxicity a reappraisal using rodents models.

Trimethyltin-induced intoxication has a great impact on human health due to the widespread occurrence of methyltin compounds. Acute TMT intoxication in humans leads to a variety of neurological symptoms which involve primarily the limbic system. In the present review we summarized the neuromorphological correlates of this neurological syndrome extending the analysis to various extra-limbic regions and detailing the fine ultrastructure of TMT-induced neuronal alterations. In order to comprehend the pathophysiology of TMT-induced neuronal damage we analysed the various experimental models of TMT-induced neurotoxicity. When comparing various animal species, it seems that the variety of neuropathological correlates are not related to species difference in the sensitivity to TMT toxicity but to a different susceptibility to secondary effects produced by TMT. In fact, apart from a primary neurotoxic damage induced by TMT at neuronal level, this compound promotes the onset of limbic and generalized seizures, which in turn add a secondary damage to that induced immediately by TMT. Thus, the different neuropathology observed in different animal species is produced mainly by a different sensitivity to epilepsy-induced brain damage.

Parkinson's disease and the gut: a well known clinical association in need of an effective cure and explanation.

Parkinson's disease (PD) is a neurodegenerative disorder which leads to severe movement impairment; however, Parkinsonian patients frequently suffer from gastrointestinal (GI) problems which at present are poorly understood, scarcely investigated, and lack an effective cure. Traditionally, PD is attributed to the loss of mesencephalic dopamine-containing neurons; nonetheless, additional nuclei, such as the dorsal motor nucleus of the vagus nerve and specific central noradrenergic nuclei, are now identified as targets of PD. While the effects of PD on the somatic motor systems are well characterized, the influence on the digestive system still needs to be clarified. Recent findings demonstrate the occurrence of pathological alterations within peripheral neuronal networks in the GI tract of Parkinsonian patients. However, it remains unclear whether a real cell loss occurs, and whether this happens specifically for a subclass of autonomic neurons or if it reflects the sole loss of autonomic nerves. This review summarizes the neurochemical and morphological changes which might be responsible for impaired GI motility. Moreover, we focus on the experimental models to reproduce the altered digestive system of Parkinsonian patients since an experimental model able to mimic such features of PD is required. In the last part of the manuscript, we suggest potential therapeutic targets.

Methamphetamine induces ectopic expression of tyrosine hydroxylase and increases noradrenaline levels within the cerebellar cortex.

Methamphetamine produces locomotor activation and typical stereotyped motor patterns, which are commonly related with increased catecholamine activity within the basal ganglia, including the dorsal and ventral striatum. Since the cerebellum is critical for movement control, and for learning of motor patterns, we hypothesized that cerebellar catecholamines might be a target of methamphetamine. To test this experimental hypothesis we injected methamphetamine into C57 Black mice at the doses of 5 mg/kg two or three times, 2 h apart. This dosing regimen is known to be toxic for striatal dopamine terminals. However, we found that in the cerebellum, methamphetamine increased the expression of the primary transcript of the tyrosine hydroxylase (TH) gene, followed by an increased expression of the TH protein. Increased TH was localized within Purkinje cells, where methamphetamine increased the number of TH-immunogold particles, and produced a change in the distribution of the enzyme by increasing the cytoplasmic percentage. Increased TH expression was accompanied by a slight increase in noradrenaline content. This effect was highly site-specific for the cortex of posterior vermal lobules, while only slight effects were detectable in the hemispheres. The present data indicate that the cerebellum does represent a target of methamphetamine, which produces specific and fine alterations of the catecholamine system involving synthesis, amount, and compartmentalization of TH as well as increased noradrenaline levels. This may be relevant for motor alterations induced by methamphetamine. In line with this, inherited cerebellar movement disorders in various animal species including humans are associated with increased TH immunoreactivity within intrinsic neurons of the same lobules of the cerebellar cortex.

Abnormal involuntary movements (AIMs) following pulsatile dopaminergic stimulation: severe deterioration and morphological correlates following the loss of locus coeruleus neurons.

Parkinsonian patients are treated with dopamine replacement therapy (typically, intermittent administration of the dopamine precursor L-DOPA); however, this is associated with the onset of abnormal involuntary movements, which seriously impair the quality of life. The molecular mechanisms underlying abnormal involuntary movements represent an intense field of investigation in the area of neurobiology of disease, although their aetiology remains unclear. Apart from the fine cellular mechanisms, the pathways responsible for the generation of abnormal involuntary movements may involve changes in neurotransmitter systems. A potential candidate is noradrenaline, since a severe loss of this neurotransmitter characterizes Parkinson's disease, and noradrenergic drugs produce a symptomatic relief of L-DOPA-induced dyskinesia. In previous studies we found that pulsatile dopamine release, in the absence of the physiological noradrenaline innervation, produces motor alterations and ultrastructural changes within striatal neurons. In the present study we demonstrate that a unilateral damage to the noradrenaline system anticipates the onset and worsens the severity of L-DOPA-induced contralateral abnormal involuntary movements in hemi-parkinsonian rats. Similarly, ubiquitin-positive striatal ultrastructural changes occur in unilaterally dopamine-depleted, noradrenaline-deficient rats following chronic L-DOPA administration. This study confirms a significant impact of the noradrenergic system in the natural history of Parkinson's disease and extends its role to the behavioural and morphological effects taking place during pulsatile dopamine replacement therapy.

A short overview on the role of alpha-synuclein and proteasome in experimental models of Parkinson's disease.

The Ubiquitin Proteasome System is a multi-enzymatic pathway which degrades polyubiquinated soluble cytoplasmic proteins. This biochemical machinery is impaired both in sporadic and inherited forms of Parkinsonism. In the present paper we focus on the role of the pre-synaptic protein alpha-synuclein in altering the proteasom based on the results emerging from experimental models showing a mechanistic chain of events between altered alpha-synuclein, proteasome impairment and formation of neuronal inclusions and catecholamine cell death.

A hypothesis on prion disorders: are infectious, inherited, and sporadic causes so distinct?

Prion diseases include a group of either sporadic, inherited or infectious disorders characterized by spongiform neurodegeneration and reactive glyosis in several brain regions. Whatever the origin, the neuropathological hallmark of prion diseases is the presence of brain aggregates containing an altered isoform of a cellular protein, named prion protein. Recent findings show the potential toxicity of the normal cellular prion protein, which occurs when its physiological metabolism is altered. In particular, several studies demonstrate that accumulation of the prion protein in the cytosol can be a consequence of an increased amount of misfolded prion proteins, a derangement of the correct protein trafficking or a reduced activity of the ubiquitin-proteasome system. The same effects can be a consequence of a mutation in the gene coding for the prion protein. In all these conditions, one assists to accumulation and self-replication of insoluble prion proteins which leads to a severe disease resembling what observed following typical "prion infections". This article provides an opinion aimed at reconciling the classic Prusiner's theory concerning the "prion concepts" with the present knowledge arising from experimental studies on neurodegenerative disorders, suggesting a few overlapping steps in the pathogenesis of these diseases.

Placental barrier breakage in preeclampsia: ultrastructural evidence.

OBJECTIVE: It is known that the placenta acts as an immunological barrier between the mother and fetal "graft" allowing two antigenically different organisms to tolerate one another. Preeclampsia may be considered as a fetal rejection consequent to severe damage at placental endothelial and syncytiotrophoblast level. In order to verify this placental barrier damage we undertook the present study by electron microscopy. STUDY DESIGN: 14 placentae from preeclaptic women, and the same number of placentae from healthy controls were examined. RESULTS: The results showed that endothelial cells from preeclamptic placentae express various and severe alterations, consisting of swollen and bulbous cytoplasm, degenerated inter-endothelial junctions with consequent crossing of fetal blood cells outside the vessels. CONCLUSIONS: These lesions could be the ultrastructural evidence of the placental barrier breakage leading to rejective reaction we presumed to be basis of preeclampsia.

Similarities between methamphetamine toxicity and proteasome inhibition.

The monoamine neurotoxin methamphetamine (METH) is commonly used as an experimental model for Parkinson's disease (PD). In fact, METH-induced striatal dopamine (DA) loss is accompanied by damage to striatal nerve endings arising from the substantia nigra. On the other hand, PD is characterized by neuronal inclusions within nigral DA neurons. These inclusions contain alpha-synuclein, ubiquitin, and various components of a metabolic pathway named the ubiquitin-proteasome (UP) system, while mutation of genes coding for various components of the UP system is responsible for inherited forms of PD. In this presentation we demonstrate for the first time the occurrence of neuronal inclusions in vivo in the nigrostriatal system of the mouse following administration of METH. We analyzed, in vivo and in vitro, the shape and the fine structure of these neuronal bodies by using transmission electron microscopy. Immunocytochemical investigation showed that these METH-induced cytosolic inclusions stain for ubiquitin, alpha-synuclein, and UP-related molecules, thus sharing similar components with Lewy bodies occurring in PD, with an emphasis on enzymes belonging to the UP system. In line with this, blockade of this multicatalytic pathway by the selective inhibitor epoxomycin produced cell inclusions with similar features. Moreover, using a multifaceted pharmacological approach, we could demonstrate the need for endogenous DA in order to form neuronal inclusions.

Effects of repeated low doses of MDMA on EEG activity and fluoro-jade B histochemistry.

The psychostimulant 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an amphetamine derivative that is widely abused. In previous studies, depending on the animal species, neurotoxicity has been demonstrated for either serotonin (5-HT) or/and dopamine (DA) nerve endings. These studies focused on the basal ganglia circuitry; however, in humans chronic abuse of MDMA often results in neurological symptoms that last after MDMA withdrawal and are not related to the extrapyramidal system such as electroencephalographic (EEG) abnormalities and cognitive impairment. These alterations might be due to the concomitant intake of other illicit compounds, the consequence of MDMA-induced hyperthermia, or to a primary neurotoxicity directed to extrastriatal regions. These observations call for a more in-depth analysis on the potential involvement of brain areas outside the basal ganglia in the toxic effects induced primarily by MDMA. In the present study, we treated C57Black mice chronically (25 days) with daily injections of MDMA (2.5 mg/kg). During treatments, mice were monitored in order to detect behavioral modifications, and epidural electrodes were installed to perform EEG recording. Behavioral data showed a sensitization as measured by locomotor activity, which related to progressive and long-lasting EEG changes and neuronal degeneration within the hippocampus.

Distribution of 3-nitrotyrosine in the nasal polyps of atopic patients.

OBJECTIVE: To investigate whether formation of nitrotyrosine in the nasal polyps of atopic patients occurs. STUDY DESIGN: A nonrandomized, retrospective, controlled qualitative and quantitative study. METHODS: Nasal polyp tissue samples were acquired from 12 atopic patients. Control fragments of nasal mucosa were taken from 10 patients undergoing corrective surgery of the nasal septum. For routine histologic examinations, hematoxylin-eosin staining was used. Low-magnification microscopy was designed to yield pathologic characteristics and high magnification to quantify the number of eosinophils in the subepithelial connective tissue. Presence of nitrotyrosine was assessed by immunohistochemical method. RESULTS: Hematoxylin-eosin staining revealed presence of numerous eosinophils in the epithelium and in the subepithelial connective tissue. All polyps were characterized by epithelial damage. Nitrotyrosine was present in the eosinophils, in the ciliated cell, and in cells of the damaged epithelium. Goblet cells, glands, and vessels were found to be negative. No significant differences concerning the localization of nitrotyrosine were recognized among the examined nasal polyps. CONCLUSIONS: Nitrotyrosine immunohistochemical staining in nasal-polyp tissues suggested the existence of progressive epithelium injury caused by peroxynitrite. Consequences of peroxynitrite formation in eosinophils remain to be precisely established. The lack of nitrotyrosine in glands and blood vessels indicated that peroxynitrite does not have a significant role in the vascular and glandular dysfunction of nasal polyps.

DNA damage and ubiquitinated neuronal inclusions in the substantia nigra and striatum of mice following MDMA (ecstasy).

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative, which is neurotoxic to both serotonin (5HT) and dopamine (DA) nerve terminals. Previous reports, carried out in rodents and non-human primates, demonstrated neurotoxicity to monoamine axon terminals, although no study has analyzed nigral and striatal cell bodies at the sub-cellular level. OBJECTIVE: In this study, we examined intrinsic nigral and striatal cells, and PC12 cell cultures to evaluate whether, in mice, MDMA might affect nigral and striatal cell bodies. METHODS: After administering MDMA, we analyzed effects induced in vivo and in vitro using high-performance liquid chromatography (HPLC) analysis, light- and electron microscopy with immunocytochemistry, and DNA comet assay. RESULTS: We found that MDMA (5 mg/kg x4, 2 h apart), besides a decrease of nigrostriatal DA innervation and 5HT loss, produces neuronal inclusions within nigral and intrinsic striatal neurons consisting of multi-layer ubiquitin-positive whorls extending to the nucleus of the cell. These fine morphological changes are associated with clustering of heat shock protein (HSP)-70 in the nucleus, very close to chromatin filaments. In the same experimental conditions, we could detect oxidation of DNA bases followed by DNA damage. The nature of inclusions was further investigated using PC12 cell cultures. CONCLUSIONS: The present findings lead to re-consideration of the neurotoxic consequences of MDMA administration. In fact, occurrence of ubiquitin-positive neuronal inclusions and DNA damage both in nigral and striatal cells sheds new light into the fine alterations induced by MDMA, also suggesting the involvement of nuclear and cytoplasmic components of the ubiquitin-proteasome pathway in MDMA toxicity.

Amphetamines induce ubiquitin-positive inclusions within striatal cells.

The present study explores whether effects induced by amphetamine derivatives on striatal GABA cells might be connected with effects on dopamine (DA) metabolism. Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") were administered to C57Black mice following a dosage regimen in which various doses of both drugs were injected i.p. at 2-h intervals. Neuronal inclusions produced under these experimental conditions were examined under electron microscopy. Drugs reducing DA availability prevented inclusion formation; conversely we observed that increasing DA synthesis or impairing physiological DA degradation enhanced the number of inclusions. The present study indicates that the presence of extracellular striatal DA is essential for the production of subcellular alterations induced by amphetamine derivatives. This is in line with a recent hypothesis connecting striatal DA release with degeneration of striatal GABA neurons.

Recent knowledge on molecular components of Lewy bodies discloses future therapeutic strategies in Parkinson's disease.

Lewy bodies (LB) were first described by Lewy in 1912 [1] as neuronal pale eosinophilic inclusions which became a pathological hallmark of Parkinson s disease (PD). In his original study, Lewy defined these inclusions as pale eosinophilic cytoplasmic structures, and studies since then have revealed LB to be ubiquitin-, alpha-synuclein-, and parkin-containing inclusions. This suggests that knowledge of the biochemical steps involved in the genesis of LB might disclose a final common pathway which might be responsible for different types of inherited and sporadic parkinsonism. This would lead to the identification of new therapeutic targets for interfering with disease progression. Although LB were originally described solely in PD, in the last decade these inclusions were described in a spectrum of degenerative disorders ranging from pure movement disorders to dementia. This suggests that common biochemical alterations leading to the formation of intracellular inclusions might underlie various pathological conditions. Consequently, the knowledge of the biochemical steps involved in the formation of neuronal inclusions could represent a key to develop new therapeutic strategies. In recent years it has been possible to develop both in vitro and in vivo neuronal inclusions resembling Lewy bodies. These experimental approaches have ranged from the use of alpha-synuclein transgenic mice to the continuous exposure to a mitochondrial complex I inhibitor. The aim of the present paper is to review briefly, recent advances on Lewy body research to achieve new insight into the etiology of PD and the molecular events leading to neurodegeneration.

Effects of repeated exposures to xenon on rat adrenal cortex ultrastructure.

Xenon has many properties of the ideal anaesthetic and it has been proposed to replace classic volatile anaesthetics. Although some studies demonstrated that xenon does not induce gross morphological changes in major organs, little is known on its possible ultrastructural effects. The present study investigates the subcellular effects of repeated exposures to 70% xenon on rat adrenal cortex in comparison with N2O. Animals were divided into four groups: xenon-exposed, N2O-exposed, sham-exposed and controls. Exposed rats were placed into a sealed cage to breathe the respective gas mixture for 2.5 h/day for a week. Specimens of adrenal cortex for electron microscopy and blood samples for determination of corticosterone plasma levels were taken at the end of the last exposure or one week after the last exposure (recovery). Adrenal cortex from N2O- and sham-exposed rats mainly showed dilation of endoplasmic reticulum, whereas xenon-exposed rats also exhibited several cells with lipid droplets appearing subdivided into smaller droplets, irregular in shape and size. In all experimental groups, corticosterone plasma levels increased in comparison to controls. Both ultrastructural and hormonal changes were not detected anymore after one week from the last exposure. These findings indicate that xenon is able to induce subcellular changes in rat adrenal cortex, mainly at the level of lipid structures. The transient changes induced by xenon suggest that this gas can be regarded as a safer anaesthetic.

Striatal postsynaptic ultrastructural alterations following methylenedioxymethamphetamine administration.

Amphetamine derivatives, such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), act as monoaminergic neurotoxins in the central nervous system. Although there are slight differences in their mechanism of action, these compounds share a final common pathway, which involves dopamine release and oxidative stress. Apart from striatal toxicity involving monoamine axons, no previous report evidenced any alteration at the striatal level concerning postsynaptic sites. Given the potential toxicity for extracellular dopamine at the striatal level, and the hypothesis for neurotoxic effects of dopamine on striatal medium-sized neurons in Huntington's disease, we evaluated at an ultrastructural level the effects of MDMA on intrinsic striatal neurons of the mouse. In this study, administering MDMA, we noted ultrastructural alterations of striatal postsynaptic GABAergic cells consisting of neuronal inclusions shaped as whorls of concentric membranes. These whorls stained for ubiquitin but not for synuclein and represent the first morphologic correlate of striatal postsynaptic effects induced by MDMA.

Noradrenergic loss enhances MDMA toxicity and induces ubiquitin-positive striatal whorls.

Movement disorders involve a number of neurodegenerative conditions, mostly affecting basal ganglia. Parkinson's disease (PD) is classically defined by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Administration of specific neurotoxins represents a common tool to reproduce this lesion. Among these, amphetamine derivatives act as powerful monoamine neurotoxins, impairing striatal dopamine (DA) axons in mice. Despite the well-investigated effects on striatal DA terminals, only sporadic studies have focused on the potential toxicity of amphetamines towards post-synaptic neurons within the striatum. In the present work we found that 3,4-methylenedioxymethamphetamine (MDMA) produces ultrastructural alterations in striatal cells, featuring as membraneous whorls, positive for ubiquitin and heat shock protein 70. These morphological alterations were enhanced in locus coeruleus-lesioned mice.

Subcellular localization of a glutathione-dependent dehydroascorbate reductase within specific rat brain regions.

Recently, we described the occurrence of a dehydroascorbate reductase within the rat CNS. This enzyme regenerates ascorbate after it is oxidized during normal aerobic metabolism. In this work, we describe the neuronal compartmentalization of the enzyme, using transmission electron microscopy of those brain areas in which the enzyme was most densely present when observed under light microscopy. In parallel biochemical studies, we performed immunoblotting and measured the enzyme activity of the cytoplasm and different nuclear fractions. Given the abundance of ascorbate in the caudate-putamen, we focused mostly on the occurrence of dehydroascorbate reductase at the striatal subcellular level. We also studied cerebellar Purkinje cells, hippocampal CA3 pyramidal cells and giant neurons in the magnocellular part of the red nucleus. In addition to neurons, immunolabeling was found in striatal endothelial cells, in the basal membrane of blood vessels and in perivascular astrocytes. In neuronal cytosol, the enzyme was observed in a peri-nuclear position and on the nuclear membrane. In addition, in both the striatum and the cerebellum, we found the enzyme within myelin sheets. Dehydroascorbate reductase was also present in the nucleus of neurons, as further indicated by measuring enzyme activity and by immunoblotting selected nuclear fractions. Immunocytochemical labeling confirmed that the protein was present in isolated pure nuclear fractions. Given the great amount of free radicals which are constantly generated in the CNS, the discovery of a new enzyme with antioxidant properties which translocates into neuronal nuclei appears to be a potential starting point to develop alternative strategies in neuroprotection.